1. Field of the Invention
The present invention relates to a screening method for a photoaging- or wrinkle-preventing or improving agent.
2. Background of the Invention
Cell aging, particularly skin aging, involves changes in appearance such as the formation of wrinkles and sags and reduction in skin elasticity. Therefore, there is a strong demand for the elucidation of an aging mechanism and for anti-aging remedy.
Heretofore, the formation of wrinkles and the like has been believed to have a strong relationship with ultraviolet rays, and skin aging caused by ultraviolet irradiation is called photoaging and has been studied in various ways. The present inventors have also reported that the elasticity of the stratum corneum, that is, epidermal elasticity, of hairless mice that have developed wrinkles due to chronic ultraviolet irradiation is significantly lower than that of unirradiated mice, indicating the relationship between wrinkles and epidermal elasticity, and that reduced keratin filament distribution (aggregation) attributed to the chronic ultraviolet irradiation was found to cause this reduction in the elasticity, resulting in the formation of wrinkles (Sano T, Kume T, Fujimura T, Kawada H, Moriwaki S, Takema Y: The formation of wrinkles caused by transition of keratin intermediate filaments after repetitive UVB exposure. Arch. Dermatol. Res. 2005; 296: 359-365).
On the other hand, the properties and functions of epidermal tissues are mostly determined and maintained by cornification, that is, the differentiation program unique to epidermal keratinocytes. The skeletal structure of the cornified cell is mechanically maintained by keratin proteins. Approximately 20 or more kinds of keratin proteins have been found out so far, of which keratin 5 (K5), keratin 14 (K14), keratin 1 (K1), and keratin 10 (K10) proteins are known to be expressed in facial skins and so on while hyperproliferative keratin proteins such as keratin 6 (K6) and keratin 16 (K16) proteins are known to be expressed in wounded or overstimulated tissues. The composition of these keratin proteins has been shown to control the mechanical properties of keratin filaments (Yamada S, Wirtz D, Coulombe P A: Pairwise assembly determines the intrinsic potential for self-organization and mechanical properties of keratin filaments. Mol. Biol. Cell. 2002; 13: 382-391; Yamada S, Wirtz D, Coulombe P A: The mechanical properties of simple epithelial keratins 8 and 18: discriminating between interfacial and bulk elasticities. J. Struct. Biol. 2003; 143: 45-55; and Paladini R D, Takahashi K, Bravo N S, Coulombe P A: Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16. J. Cell Biol. 1996; 132: 381-397).
However, the detailed relationship between skin photoaging or wrinkle formation and keratin proteins has not been elucidated.